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K J Ryan

Publications and source records attributed to K J Ryan.

At least 37 records · Page 2Linked to original sources
PubMed1990

Inhibition of nucleoside transport by nitrobenzylthioformycin analogs.

The formycin analogs of nitrobenzylthioinosine and nitrobenzylthioguanosine were synthesized and evaluated as nucleoside transport inhibitors. These analogs have a potential therapeutic advantage over their parent compounds in that their C-nucleosidic linkages prevent them from being degraded to the immunosuppressive agents, 6-mercaptopurine and 6-thioguanine. 7-[(4-Nitrobenzyl)-thio]-3-(beta-D-ribofuranosyl)pyrazolo[4,3- d]pyrimidine (NBTF) and 5-amino-7-[(4-nitrobenzyl)thio]-3-(beta-D- ribofuranosyl)pyrazolo[4,3-d]pyrimidine (NBTGF) were inhibitors of nucleoside transport in human erythrocytes and HL-60 leukemia cells. The IC50 value for nitrobenzylthioinosine, NBTF and NBTGF with 10% erythrocyte suspensions were 18, 18 and 40 nM respectively. Specific binding studies with [3H]NBTF yielded a Kd of 3.4 nM with erythrocytes, approximately 10-fold higher than values reported for nitrobenzylthioinosine. NBTF and nitrobenzylthioinosine bound to HL-60 cells with Kd values of 8.1 and 0.81 nM respectively. The octanol/water partition coefficients of nitrobenzylthioinosine, NBTF and NBTGF were 3.5, 3.2, and 2.8 respectively. NBTF could be expected to be equipotent with nitrobenzylthioinosine in whole blood where inhibitor concentrations of 10(-7) to 10(-6) M are required in order to saturate erythrocytic binding sites; hence, it may exhibit the advantages inherent in a C-nucleoside.

Adenosine↗
PubMed1990

Molecular epidemiology of Shigella sonnei in Pima County, Arizona: evidence for a Mexico-related plasmid.

In 1984, the incidence of shigellosis was 32.4 per 100,000 population in Pima County, Arizona. To investigate sources, Shigella isolates and epidemiologic data were collected for 79 cases of infection with Shigella sonnei, the most common species. Since S. sonnei has a single serotype, plasmid isolation was attempted to refine the epidemiologic analysis. There were seven plasmid patterns containing 17, 13, 4, 22, 9, 2, and 3 isolates. Twelve of 17 isolates associated with recent travel to Mexico were in a group distinguished by a 5.1-kilobase (kb) plasmid. This plasmid was used to probe Southern blots of plasmids from strains of all groups. The Mexico-related plasmid probe hybridized to all the 5.1-kb plasmids and to 5.5- and 7.4-kb plasmids from three other groups. Of the 79 isolates, 50 contained plasmids homologous to the Mexico-related plasmid probe, suggesting association with travel to Mexico.

Arizona↗
PubMed1990

Interpregnancy interval and risk of preterm labor.

In 1977-1980, over 12,000 pregnant women being followed at the Boston Hospital for Women were interviewed and had their medical records reviewed. The effect of interpregnancy interval on the risk of preterm labor was estimated in 4,467 of these women whose previous pregnancy had resulted in a full-term live birth. The rate of preterm birth after the spontaneous onset of labor in this cohort was 3.8 percent. While the possibility of an increased risk of preterm labor for interpregnancy intervals of 3 months or less cannot be definitely excluded (adjusted odds ratio = 2.0, 95 percent confidence interval 0.7-5.4), no relation was found between other interpregnancy intervals and the risk of preterm labor. Earlier work from this same cohort showed a strong negative association between interpregnancy interval and small-for-gestational-age birth. Combining this with the results from the present study reinforces the importance of differentiating low birth weight due to preterm birth from that due to intrauterine growth retardation.

Birth Intervals↗
PubMed1989

Birth-day choices.

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Delivery, Obstetric↗
PubMed1989

Western blot analysis of porcine corpus luteum heparin binding proteins using antibodies to acidic and basic fibroblast growth factor.

The 105,000 X g supernatant from homogenates of porcine corpora lutea was chromatographed on a heparin Sepharose affinity column. Bound protein was batch eluted and analyzed on Western blots using antibodies to acidic and basic fibroblast growth factor (FGF). The antibody to acidic FGF reacted specifically with at least four protein bands ranging from 21 to 50 kDa. Three antibodies to human basic FGF (145 residues) generated against either the N-terminal sequence (1-12), the internal sequence (33-43), or the C-terminal end (135-145) also reacted specifically with a total of four different bands. The apparent molecular weights ranged between 20 and 55 kDa. The luteal extract also expressed message for acidic FGF. The results show that there may exist a family of FGF-like molecules in the corpus luteum and demonstrates for the first time the presence of acidic FGF in that tissue.

Animals↗
PubMed1989

The association of inter-pregnancy interval with small for gestational age births.

The association between small for gestational age (SGA) birth at term and inter-pregnancy interval was examined in a hospital cohort of 4489 multiparous women. The greatest risk of SGA birth was found in women with the shortest inter-pregnancy intervals. Even after adjusting for multiple confounding factors, women whose inter-pregnancy interval was 18 or fewer months (over one-third of women in the cohort) remained at twice the risk of giving birth to a term SGA infant when compared with women whose inter-pregnancy interval was 24-36 months. In a logistic regression analysis examining the occurrence of SGA birth in women with inter-pregnancy intervals of 36 months or less, a strong linear association was noted between these two factors. The association of term SGA birth with short inter-pregnancy interval could result from one or more physiologic factors that might act to limit fetal growth. In that case, short inter-pregnancy interval would represent a potentially preventable cause of SGA birth.

Birth Intervals↗
PubMed1988

Association of maternal hematocrit with premature labor.

An examination of the association of maternal hematocrit with the occurrence of premature birth revealed a continuous relationship between these two factors with an increasing rate of prematurity occurring with decreasing maternal hematocrit. The lowest risk of premature birth was found when maternal hematocrit was between 41% and 44%. Statistically increases in prematurity were noted at all hematocrit levels of less than or equal to 38%. A woman with a hematocrit of 37% had twice the risk of having a premature birth as a woman whose hematocrit was between 41% and 44% (p less than 0.01). In a logistic regression analysis with premature birth as the dependent variable and hematocrit as the only predictor variable, it was noted that decreasing the hematocrit by a single point was associated with a 24% increase in the risk of prematurity (odds ratio = 1.24) while a five-point decrease in hematocrit was associated with a tripling in the risk of prematurity (odds ratio = 2.98). In a multivariable logistic regression analysis hematocrit was noted to explain more of the variation in prematurity than any of the other risk factors included in the model. An investigation of this association in specific groups at high risk of having premature births revealed that 46% of the increased risk of prematurity in black women and 49% of the increased risk of prematurity in women receiving welfare was related to hematocrit or some factor associated with hematocrit.

Adult↗
PubMed1988

Immunoreactive substance P in the human ovary.

Although substance P has been demonstrated in the nonhuman ovary, it has not previously been identified in normal human ovarian tissue. We examined ovarian surgical specimens from 30 women for the presence of immunoreactive substance P. With the use of a specific radioimmunoassay, immunoreactive substance P was identified in these ovarian extracts. The geometric mean of the immunoreactive substance P concentration was 0.55 pg/mg wet weight (95% confidence limits 0.04 and 6.15). Thecal and stromal concentrations of immunoreactive substance P were greater than those in the corpora lutea and tunica albuginea. Large follicles had a lower concentration of immunoreactive substance P than did small follicles. We conclude that the neuropeptide substance P is present in some normal human ovaries and may be a modulator of ovarian function.

Adult↗
PubMed1988

Rat Leydig cell and granulosa cell 17-ketosteroid reductase activity: subcellular localization and substrate specificity.

The potent gonadal steroids testosterone and estradiol are synthesized from the biologically weak precursors, androstenedione and estrone, by enzymatic reduction of the ketone group at carbon-17 of the steroid nucleus (17-ketosteroid reductase). To test the hypothesis that Leydig and granulosa cells may contain a distinct 17-ketosteroid reductase enzyme, the subcellular localization and the substrate specificity of the enzyme was examined in each cell type. In Leydig cells, the 17-ketosteroid reductase activity was concentrated in the microsomal fraction of the cell. In granulosa cells, the 17-ketosteroid reductase activity was concentrated in the cytosolic fraction of the cell. In Leydig cell microsomes, the apparent Michaelis-Menten constant for the conversion of androstenedione to testosterone was 0.41 mumol/L and for the conversion of estrone to estradiol it was 12 mumol/L. In granulosa cell cytosol, the apparent Michaelis-Menten constant for the conversion of estrone to estradiol was 1.1 mumol/L and for the conversion of androstenedione to testosterone it was 15 mumol/L. These results demonstrate that rat Leydig and granulosa cells each contain a 17-ketosteroid reductase enzyme with unique subcellular localization and substrate specificity.

17-Hydroxysteroid Dehydrogenases↗
PubMed1988

The role of hyperinsulinemia in the pathogenesis of ovarian hyperandrogenism.

The evidence that supports the hypothesis that insulin and LH both regulate ovarian androgen production was presented. The most dramatic clinical example of the association between hyperinsulinemia and hyperandrogenism is the HAIR-AN syndrome. Our hypothesis is that, in the HAIR-AN syndrome, the severe insulin resistance causes a compensatory hyperinsulinemia, which stimulates ovarian androgen production if adequate LH is present. The acanthosis nigricans is an epiphenomenon of the syndrome. Acanthosis nigricans is a dermatologic manifestation of severe insulin resistance. In vitro evidence suggests that insulin and IGF-I stimulate androgen production in incubations of human stroma and theca. The stromatropic effects of insulin may sensitize the stroma to the stimulatory effects of LH. In some hyperandrogenic-insulin-resistant women, a glucose load appears to produce an acute rise in circulating androgens. The magnitude of the rise in circulating androgens is proportional to the magnitude of the insulin response to the glucose load. These data suggest that hyperinsulinemia may play a central role in the development of ovarian hyperandrogenism.

Acanthosis Nigricans↗
PubMed1988

Adverse outcomes of pregnancy in women exposed to diethylstilbestrol in utero.

We analyzed data collected by interview and medical record review for 200 women exposed to diethylstilbestrol (DES) and 12,240 unexposed women to evaluate the relation between maternal DES exposure and outcomes of pregnancy. Low birth weight, short gestation, bleeding in the first trimester, toxemia, breech presentation and premature rupture of the membranes occurred more often among the exposed women. These relationships remained statistically significant after the use of linear regression and logistic regression analyses to control for multiple confounding factors. Both exposed women and their physicians should be aware of the possible relationship between maternal exposure to DES and late adverse outcomes of pregnancy. Close medical supervision of these women throughout pregnancy and delivery is recommended.

Demography↗
PubMed1987

Risk factors accounting for racial differences in the rate of premature birth.

In a hospital-based cohort of 8903 black and white women, we investigated medical and socioeconomic risk factors that may explain the known increase in premature births among black women. Among the medical conditions examined, only the maternal hematocrit level (or some related factor) explained a substantial proportion (60 percent) of the increased rate of premature births to black women. Four economic, demographic, and behavioral predictors of prematurity were also examined: age less than 20 years, single marital status, receiving welfare support, and not having graduated from high school. The number of these socioeconomic risk factors occurring in a woman was strongly predictive of premature birth of her infant, regardless of the particular risk factors present. The presence of any one factor was associated with a moderate increase in the risk of prematurity (7.0 percent as compared with 4.6 percent with no risk factors present); the presence of two or more characteristics was associated with a much higher risk (11.2 percent). When the number of these four risk factors pertaining to an individual woman was taken into account, race was no longer a significant predictor of premature birth (odds ratio, 1.22; 95 percent confidence interval, 0.94 to 1.59). When both the maternal hematocrit level and the number of the four socioeconomic risk factors were taken into account, essentially all of the racial variation in prematurity was explained, with the odds ratio for prematurity among blacks being 1.03 (95 percent confidence interval, 0.79 to 1.35). We conclude that the racial difference in the rate of premature birth is attributable to specific medical and socioeconomic characteristics.

Adult↗